Agricultural Antibiotics Research Articles

Toxicity Study of Sulfonamides Antibiotics

Antibiotics refer to organic substances produced by plants, animals, microorganisms and other organisms in the course of their life activities or obtained by other methods, which can selectively inhibit or affect other organisms at low concentrations. According to the chemical structure, sulfonamides (SAs), tetracycline, etc. can be divided into sulfonamides, and veterinary antibiotics, agricultural antibiotics, medical antibiotics, etc. can be divided into sulfonamides according to the source. Antibiotics can inhibit cell growth and reproduction, and have been continuously synthesized since the advent of penicillin in 1929. At present, antibiotics have become one of the most widely used and used drugs in the world, not only for the prevention and treatment of human and animal diseases, but also as animal feed.

The Biological Activities of Polyether Ionophore Antibiotic Routiennocin is Independent of Absolute Stereochemistry.

Carboxylic polyether ionophores (CPIs) are among the most prevalent agricultural antibiotics (notably in the US) and these compounds have been in use for decades. The potential to reposition CPIs beyond veterinary use, e. g. through chemical modifications to enhance their selectivity window, is an exciting challenge and opportunity, considering their general resilience towards resistance development. Given the very large societal impact of these somewhat controversial compounds, it is surprising that many aspects of their mechanisms and activities in cells remain unclear. Here, we report comparative biological activities of the CPI routiennocin and two stereoisomers, including its enantiomer. We used an efficient convergent synthesis strategy to access the compounds and conducted a broad survey of antibacterial activities against planktonic cells and biofilms as well as the compounds' effects on mammalian cells, the latter assessed both via standard cell viability assays and broad morphological profiling. Interestingly, similar bioactivity of the enantiomeric pair was observed across all assays, strongly suggesting that chiral interactions do not play a decisive role in the mode of action. Overall, our findings are consistent with a mechanistic model involving highly dynamic behaviour of CPIs in biological membranes.

Regulatory fine-tuning of mcr-1 increases bacterial fitness and stabilises antibiotic resistance in agricultural settings

Antibiotic resistance tends to carry fitness costs, making it difficult to understand how resistance can be maintained in the absence of continual antibiotic exposure. Here we investigate this problem in the context of mcr-1, a globally disseminated gene that confers resistance to colistin, an agricultural antibiotic that is used as a last resort for the treatment of multi-drug resistant infections. Here we show that regulatory evolution has fine-tuned the expression of mcr-1, allowing E. coli to reduce the fitness cost of mcr-1 while simultaneously increasing colistin resistance. Conjugative plasmids have transferred low-cost/high-resistance mcr-1 alleles across an incredible diversity of E. coli strains, further stabilising mcr-1 at the species level. Regulatory mutations were associated with increased mcr-1 stability in pig farms following a ban on the use of colistin as a growth promoter that decreased colistin consumption by 90%. Our study shows how regulatory evolution and plasmid transfer can combine to stabilise resistance and limit the impact of reducing antibiotic consumption.

Research progress in biological control of tomato bacterial wilt.

Bacterial wilt caused by the infection of Ralstonia solanacearum, is one of the most harmful diseases to tomatoes, one of the most important greenhouse vegetables in China. R. solanacearum can survive and remain active in the deep soil for a long time, and the chemical control of tomato bacterial wilt is consequently limited. In this study, we introduced the characteristics of tomato bacterial wilt disease and the types of R. solanacearum, and systematically reviewed the research progresses of biological control methods from the aspects of botanical insecticides, agricultural antibiotics, biocontrol bacteria. We emphatically introduced the principle and current status of these methods, discussed the limitations and the improvement strategies, and prospected a new environmental protection and efficient biological control system based on micro-ecological regulation would be the development direction of biological control of tomato bacterial wilt.

Design, synthesis, and antimicrobial evaluation of 2-aminothiazole derivatives bearing the 4-aminoquinazoline moiety against plant pathogenic bacteria and fungi.

To find more effective agricultural antibiotics, a class of new 2-aminothiazole derivatives containing the 4-aminoquinazoline moiety were synthesized and evaluated for their antimicrobial properties against the phytopathogenic bacteria and fungi of agricultural importance. All the target compounds were fully characterized by 1 H NMR, 13 C NMR, and HRMS spectra. The bioassay results showed that compound F29 with a 2-pyridinyl substituent exhibited an outstanding antibacterial effect against Xanthomonas oryzae pv. oryzicola (Xoc) in vitro, having an EC50 (half maximal effective concentration) value as low as 2.0 μg/mL (over 30-fold more effective than the commercialized agrobactericide Bismerthiazol, with an EC50 value of 64.3 μg/mL). Additionally, compound F8 with a 2-fluorophenyl group demonstrated a good inhibitory activity towards the bacterium Xanthomonas axonopodis pv. citri (Xac), around 2-fold more active than Bismerthiazol in terms of their EC50 values (22.8 vs 71.5 μg/mL). Interestingly, this compound also demonstrated a notable fungicidal effect against Phytophthora parasitica var. nicotianae, with a largely comparable EC50 value to the commercialized fungicide Carbendazim. Finally, the mechanistic studies revealed that compound F29 exerted its antibacterial effects by increasing the permeability of bacterial membranes, reducing the release of extracellular polysaccharides, and triggering morphological changes of bacterial cells. Compound F29 held the promising potential as a lead compound for developing more efficient bactericides to fighting against Xoc. This article is protected by copyright. All rights reserved.

Evaluation of Resistance of Phytopathogenic Bacteria to Agricultural Antibiotics

Agricultural antibiotics are widely used to inhibit the growth of phytopathogenic bacteria involved in plant diseases. However, continuous antibiotic overuse in crop production may lead to the development of antibiotic resistance in phytopathogenic bacteria. This study was conducted to evaluate the resistance to three different agricultural antibiotics (oxytetracycline+streptomycin, streptomycin, and validamycin A) in 91 strains of phytopathogenic bacteria including <i>Pectobacterium carotovorum</i>, <i>Pseudomonas syringae</i> pv. <i>actinidiae</i>, <i>Clavibacter michiganensis</i> subsp. <i>michiganensis</i>, <i>C. michiganensis</i> subsp. <i>capsici</i>, and <i>Xanthomonas arboricola</i> pv. <i>pruni</i>. Bacterial growth in the presence of various concentrations of validamycin A was also assessed spectrophotometrically by analyzing the optical density. All strains did not grow when the cells were exposed to oxytetracycline+streptomycin or 100× of streptomycin. However, among the 91 strains, 4% and 2% strains showed bacterial growth at the concentrations of 1× and 10× of streptomycin, respectively. Furthermore, 97%, 93%, and 73% strains were resistant to the 1×, 10×, and 100× of validamycin A, respectively, and especially, <i>P. carotovorum</i> contained the highest resistance to the validamycin A. Minimum bactericidal concentration values of validamycin A did not correlate with the patterns of agricultural antibiotic resistance. Further studies are needed to understand the incidence and development of antibiotic resistance in phytopathogenic bacteria.

Using Only as Needed: California Limits on Agricultural Antibiotics May Bring Relief from Resistant Infections.

Using Only as Needed: California Limits on Agricultural Antibiotics May Bring Relief from Resistant Infections.

Antifungal and antifeedant terpenoids from Paraphaeosphaeria sp. cultured by extract of host Ginkgo biloba

Five undescribed terpenoids including a polyketide-terpenoid hybrid paraphaone, and four eremophilane sesquiterpenoids, paraphaterpenes A-D, as well as two known compounds were isolated from the endophytic fungus Paraphaeosphaeria sp. cultured by extract of host Ginkgo biloba L. The structures were established by spectroscopic analyses, and the single-crystal X-ray diffraction. The antifungal activity of Paraphaeosphaeria sp. cultured by extract of G. biloba against the plant pathogen Alternaria alternata was significant and higher than that of PDB medium. Tested compounds indicated antifeedant activities against silkworms with feeding deterrence index at 10–70%. Paraphaone, paraphaterpenes A, C, D and alternariol methyl ether showed significant antifungal activities against the phytopathogens A. alternata, Aspergillus fumigatus, and entomopathogen Beauveria bassiana with MICs ≤4 μg/mL. And the preliminary structure-activity relationship of eremophilane sesquiterpenoids was exhibited. The culture of Paraphaeosphaeria sp. by host G. biloba medium afforded agricultural antibiotics.

Antibiotic governance and use on commercial and smallholder farms in eastern China.

China is one of the largest consumers of agricultural antibiotics in the world. While the Chinese government has been tightening its regulations to control antimicrobial resistance (AMR) from animal sources in recent years, the extent of antimicrobial oversight and the practices of antibiotic use in animal agriculture in China has not yet been explored. This study describes the practices of antimicrobial management in eastern China and current scenarios of antibiotic use in commercial farms and smallholder backyard farming. 33 semi-structured interviews were conducted with government agriculture officials, veterinary drug sellers, farmers and smallholders in two contrasting areas of rural Zhejiang and Jiangsu provinces, China. Interview transcripts were analyzed in NVivo12 using a thematic approach. Findings revealed that although the governance of antibiotic use has made progress, especially in controlling irrational antibiotic use in commercial farms, smallholders are under-regulated due to a lack of resources and assumptions about their marginal role as food safety governance targets. We also found that smallholders resort to human antibiotics for the treatment of backyard animals because of economic constraints and lack of access to professional veterinary services. More attention needs to be devoted to the local structural needs of farmers to reduce antibiotic misuse. Considering the extensive links of AMR exposure under the One Health framework, efforts to integrate smallholders in antibiotic governance are required to address the AMR burden systematically in China.

Strategies for Solving the Issue of Malachite Green Residues in Aquatic Products: A Review

Malachite green (MG) residue in aquatic products is a widely concerning issue, and the possible source of MG contamination includes its illegal usage and environmental pollution. A variety of strategies for solving such a problem have been proposed, and the research about them is summarized in this review. The MG contamination in aquaculture environments can be eliminated by adsorption, degraded by advanced oxidation processes (AOPs), or biodegraded by microbes or enzymes. The illegal usage of MG can be prevented by screening novel anti-Saprolegnia sp. agents from current available agricultural antibiotics, plant extracts, or antagonistic microbes. Nevertheless, deficiencies also existed in these proposed solving strategies. Therefore, further research opportunities in such areas were provided. This includes developing effective combinatorial methods (adsorption + AOPs or biodegradation) for eliminating MG from the aquaculture environment; systematically considering the impact of practical conditions on the efficiency of MG elimination; screening more efficient anti-Saprolegnia sp. agents; and systematically evaluating both the in vivo activities and safety of these agents.

Antimicrobial and Cytotoxic Activity of Endophytic Fungi from Lagopsis supina.

In this study, five endophytic fungi belonging to the Aspergillus and Alternaria genera were isolated from Lagopsis supina. The antimicrobial activity of all fungal fermented extracts against Staphylococcus and Fusarium graminearum was tested using the cup-plate method. Among them, Aspergillus ochraceus XZC-1 showed the best activity and was subsequently selected for large-scale fermentation and bioactivity-directed separation of the secondary metabolites. Four compounds, including 2-methoxy-6-methyl-1,4-benzoquinone (1), 3,5-dihydroxytoluene (2), oleic acid (3), and penicillic acid (4) were discovered. Here, compounds 1 and 4 displayed anti-fungal activity against F. graminearum, F. oxysporum, F. moniliforme, F. stratum, Botrytis cinerea, Magnaporthe oryzae, and Verticillium dahliae with diverse MIC values (128-512 μg/ml), which were close to that of the positive control antifungal, actidione (64-128 μg/ml). Additionally, compounds 1 and 4 also exhibited moderate antibacterial activity against S. aureus, Listeria monocytogenes, Escherichia coli, and Salmonella enterica, with low MIC values (8-64 μg/ml). Moreover, compounds 1 and 4 displayed selective cytotoxicity against cancer cell lines as compared with the normal fibroblast cells. Therefore, this study proposes that the endophytic fungi from L. supina can potentially produce bioactive molecules to be used as lead compounds in drugs or agricultural antibiotics.

Impact of “sachet water” microplastic on agricultural soil physicochemistry, antibiotics resistance, bacteria diversity and function

Nigeria's most consumed potable water plastic wastes are indiscriminately dumped into agricultural soil despite their ability to become microplastics. The study evaluates the potential impacts of these microplastics on soil physico-chemical parameters, soil bacterial diversity and functions as well as antibiotic resistance. Soil sample was collected using a sterile hand-held auger and its physico-chemical parameters evaluated. Baseline microplastic concentration was determined via the flotation method while microbial isolates were obtained from the test (enriched with microplastics) and control samples using cultural technique and metagenomics. Metagenomic next-generation sequencing (mNGS) was done using the Illumina Miseq platform. The cluster of orthologous genes (COG) tool was used in the prediction of bacterial functional roles. Replicate readings were analysed using analysis of variance (ANOVA) and means compared using the student’s t test. Observed baseline microplastic concentration was 0.08 particles/g of soil. The addition of the microplastics to the soil sample decreased the concentrations of some metals (iron, zinc, lead and nickel) while cobalt concentration, pH level and microbial counts increased. Microbial count and pH clustered together while iron, magnesium, nitrate, nitrite, chromium, cobalt, total organic carbon, zinc, lead, and nickel showed positive loading values suggesting that the addition of microplastics could alter them. Dominant taxa were proteobacteria, unknown, firmicutes at the phyla level. At the level of species, Pseudomonas species dominated microplastics incubated soil while potential pathogenic species such as Klebsiella dominated the control sample. A higher level of multi-drug resistance and altered metabolisms was observed in the test sample. Sachet water microplastics could have serious implications for public health and food security.

Photodegradation Behavior of Agricultural Antibiotic Oxytetracycline in Water

Due to their overuse in agriculture, antibiotics are discharged into the aquatic environment, which poses a threat to human health and aquatic organisms. The agricultural antibiotic oxytetracycline (OTC) persists in aquatic media for a long time due to its resistance to biological degradation. Photolysis is a main pathway for its degradation in the natural environment and wastewater treatment, and thus, the photolysis of OTC should be investigated. In this study, the effects of reaction conditions such as the irradiation conditions, the initial OTC concentration, and the water matrix on OTC photolysis were investigated. The most efficient degradation was observed when UV-C was used as the irradiation source (k = 0.0148 ± 0.0008 min−1), and the removal ratio increased with higher light intensity. A lower initial OTC concentration and higher solution temperature were advantageous for the degradation of OTC. The presence of humic acid or inorganic ions negatively affected the degradation rate of OTC. In addition to the effects of the reaction conditions, the degradation kinetics of OTC in actual agricultural water and the photolysis of various antibiotics such as streptomycin, validamycin A, and oxolinic acid were further studied. This work proved that various factors could decrease the photodegradation of OTC, which raises the potential risks that are associated with the persistent use of antibiotics in the water environment. Therefore, the results of the present study can help to provide an understanding of the effects of various reaction conditions on the degradation of agricultural antibiotics.

Screening of a high-yield strain of avermectin B1a by colony analysis in situ.

Avermectin, an agricultural antibiotic, is widely used as an agricultural insecticide and an important lead compound of antibiotics. It is manufactured by Streptomyces avermitilis through fermentation. Manufacturers pay special attention to screening for strains with high fermentation capacity based on morphological properties of the colony and by the result of shake flask fermentation. These traditional screening methods are time-consuming and labor-intensive and require specialized equipment. Moreover, evaluation of colony appearance is highly subjective. To improve and accelerate the screening process, we developed a rapid in situ screening method. Forty-four strains isolated naturally from the spores of industrial high-yielding strains were studied. The data show that the colony fermentation titer is highly correlated with the yield from the shake flask fermentation of avermectin, and the Pearson's R is 0.990. The total titer of avermectins by shake flask fermentation is also highly correlated with the B1a titer (Pearson's R is 0.994). This result also shows that strains can be quickly screened by analyzing the colony titer. Pigment rings of the colonies that appeared after growing and maturing on the new medium plate were analyzed. The chosen colonies were directly marked and punched and then extracted with methanol. The fermentation ability can be evaluated by measuring the absorbance at 245nm. This methodology can be applied in both natural breeding and mutation breeding conditions. By continuously breeding from 2008 to 2020, the flask titer of avermectin B1a increased from 4582 ± 483 to 9197 ± 1134μg/mL.

Effects of Natural Rheum tanguticum on the Cell Wall Integrity of Resistant Phytopathogenic Pectobacterium carotovorum subsp. Carotovorum.

The abuse of agricultural antibiotics has led to the emergence of drug-resistant phytopathogens. Rifampicin and streptomycin and streptomycin resistance Pectobacterium carotovorum subsp. carotovorum (PccS1) was obtained from pathological plants in a previous experiment. Rheum tanguticum, derived from the Chinese plateau area, exhibits excellent antibacterial activity against PccS1, yet the action mode has not been fully understood. In present text, the cell wall integrity of the PccS1 was tested by the variation of the cellular proteins, SDS polyacrylamide gel electrophoresis (SDS-PAGE), scanning electron microscopy (SEM) and Fourier transform infrared spectrophotometer (FTIR) characteristics. Label-free quantitative proteomics was further used to identify the DEPs in the pathogen response to treatment with Rheum tanguticum Maxim. ex Balf. extract (abbreviated as RTMBE). Based on the bioinformatics analysis of these different expressed proteins (DEPs), RTMBE mainly inhibited some key protein expressions of beta-Lactam resistance, a two-component system and phosphotransferase system. Most of these membrane proteins were extraordinarily suppressed, which was also consistent with the morphological tests. In addition, from the downregulated flagellar motility related proteins, it was also speculated that RTMBE played an essential antibacterial role by affecting the swimming motility of the cells. The results indicated that Rheum tanguticum can be used to attenuate the virulence of the drug-resistant phytopathogenic bacteria.

Reversible addition‐fragmentation chain transfer polymerization for fabrication of polymer cations‐adjustable porous materials with excellent antibacterial activity

AbstractThe reversible addition‐fragmentation chain transfer polymerization (RAFT) is an effective method to control chain growth and regulate active centers in functional materials. Herein, a novel antibacterial material, polymer cations‐adjustable porous materials (PCaPM), was successfully synthesized by RAFT and quaternization. First, using 2‐(dodecylsulfanylthiocarbonylsulfanyl)‐2‐methylpropionic acid as the chain transfer agent of RAFT, methyl methacrylate and 2‐(dimethylamino)ethyl methacrylate as comonomers, and ethylene dimethacrylate as crosslinking agent, the light‐yellow crosslinked block copolymer (PM‐PDE), was synthesized by RAFT polymerization. Second, a series of porous materials (PCaPM) were obtained by quaternization of PM‐PDE with alternative alkyl halide and swelling effects in water. The composition and structure of PM‐PDE and PCaPM were characterized by scanning electron microscope, energy dispersive spectrometer, Fourier transform infrared spectra, 1H‐NMR, Brunauer–Emmett–Teller, and X‐ray photoelectron spectroscopy. Their antibacterial properties were also evaluated against Staphylococcus aureus, Escherichia coli, and Valsa mali. Remarkably, PCaPM, containing tertiary amine and possessing high porosity and large specific surface area, presented excellent antibacterial activity. Hence, the resultant PCaPM exhibited excellent antibacterial activity due to the quaternary ammonium salts groups, which has great prospects in application in medical treatment, agricultural antibiotic, emulator, and sewage treatment.

Discovery of Phytoalexin Camalexin and Its Derivatives as Novel Antiviral and Antiphytopathogenic-Fungus Agents

In response to the invasion of plant viruses and pathogenic fungi, higher plants produce defensive allelochemicals. Finding candidate varieties of botanical pesticides based on allelochemicals is one of the important ways to create efficient and green pesticides. Here, a series of camalexin derivatives based on a phytoalexin camalexin scaffold were designed, synthesized, and assessed for their antiviral and fungicidal activities systematically. Most of these camalexin derivatives exhibited better antiviral activities against tobacco mosaic virus (TMV) than the control antiviral agent ribavirin. Under the same test conditions, the anti-TMV activities of compounds 3d, 5a, 5d, and 10f-10h were found to be equivalent to or better than that of ningnanmycin, an agricultural cytosine nucleoside antibiotic with excellent protective effect. The antiviral mechanism research showed that compound 5a could cause 20S CP disk fusion and disintegration, thus affecting the assembly of virus particles. The results of molecular docking indicate that there were obvious hydrogen bonds between compounds 3d, 5a, and 10f and TMV CP. The binding constants of compounds 5a and 10f to TMV CP were also calculated using fluorescence titration. These camalexin derivatives also presented broad spectrum fungicidal activities, especially for Rhizoctonia solani and Physalospora piricola. In this work, the design, synthesis, structure optimization, and mode of action of camalexin derivatives were carried out progressively. This work provides a reference for using defensive chemical compounds as novel pesticide lead compounds.

BIOLOGICAL CONTROL OF TOMATO PHYTOPATHOGENS AS AN ALTERNATIVE TO AGRICULTURAL DEFENSIVES AND ANTIBIOTICS

The tomato ( Solanum lycopersicum L.) is one of the most cultivated vegetable in the world. China represents about 25 % of all world production, so there is a dependence and constant use of agricultural defensives in tomato crops. The application of chemical products banned in many parts of the world has as a side effect a major impact on human health and the ecosystem, therefore necessary to adopt other disease prevention strategies. Another method of combating tomato diseases is the use of microorganisms as a form of biological control, which is considered an alternative to agricultural defensives and antibiotics offering better sustainability and less toxicity. In this work, the agricultural defensives most used by producers were, Pyraclostrobin, Mancozebe, Copper oxychloride, and derivatives of DDT. For the antibiotics, Streptomycin and Oxytetracycline were the most used, whereas Bacillus spp. and Lactic Acid Bacteria (LAB) was the microorganisms most cited as a form of biological control. Lastly the main phytopathogens of tomato were Xanthomonas spp., Clavibac t er michiganensis subsp. michiganensis and Ralstonia solanacearum . The objectives of this work were to identify the main types of agricultural defensives, antibiotics, and genera of microorganisms used to control tomato diseases and to compare their impact on human health and the environment.

Dysregulation of ClpP by Small-Molecule Activators Used Against Xanthomonas oryzae pv. oryzae Infections.

Rice bacterial leaf blight caused by Xanthomonas oryzae pv. oryzae (Xoo) is considered a destructive plant bacterial disease. The looming crisis of antibiotic resistance necessitates the discovery of antibiotics with new modes of action. Activated caseinolytic protease P (ClpP) can degrade bacterial FtsZ proteins that are essential for cell division; thus, we hypothesized that small-molecule-induced dysregulation of XooClpP may result in degradation of XooFtsZ to treat leaf blight diseases. In this work, we have determined the crystal structures of XooClpP, and its mutant bound with ADEP4, which revealed the action modes of XooClpP assemblies and XooFtsZ degradation by dysregulated XooClpP in the presence of small-molecule activators, such as ONC212 and ADEP4. Additionally, an antibacterial assessment demonstrated that ONC212 displays excellent activity against Xoo and prevents rice bacterial leaf blight in vivo. Thus, these unique antibacterial effects of small-molecule activators of XooClpP represent a potential strategy for the development of agricultural antibiotics by targeting bacterial ClpP.

Novel carbazole-oxadiazoles as potential Staphylococcus aureus germicides

Staphylococcus aureus resistance poses nonnegligible threats to the livestock industry. In light of this, carbazole-oxadiazoles were designed and synthesized for treating S. aureus infection. Bioassay discovered that 3,6-dibromocarbazole derivative 13a had effective inhibitory activities to several Gram-positive bacteria, in particular to S. aureus, S. aureus ATCC 29213, MRSA and S. aureus ATCC 25923 (MICs = 0.6–4.6 nmol/mL), which was more active than norfloxacin (MICs = 6–40 nmol/mL). Subsequent studies showed that 3,6-dibromocarbazole derivative 13a acted rapidly on S. aureus ATCC 29213 and possessed no obvious tendency to induce bacterial resistance. Further evaluations indicated that 3,6-dibromocarbazole derivative 13a showed strong abilities to disrupt bacterial biofilm and interfere with DNA, which might be the power sources of antibacterial performances. Moreover, 3,6-dibromocarbazole derivative 13a also exhibited slight cell lethality toward Hek 293 T and LO2 cells and low hemolytic toxicity to red blood cells. The above results implied that the active molecule 13a could be studied in the future development of agricultural available antibiotics.